Jump to content

Osteoporosis

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by NeilN (talk | contribs) at 17:49, 13 March 2008 (Reverted 1 edit by 69.36.63.140 identified as vandalism to last revision by TamePhysician. using TW). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Osteoporosis
SpecialtyRheumatology Edit this on Wikidata

Osteoporosis is a disease of bone that leads to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. Osteoporosis is defined by the World Health Organization (WHO) in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old healthy female average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture.[1] Osteoporosis is most common in women after the menopause, when it is called postmenopausal osteoporosis, but may also develop in elderly men, and may occur in anyone in the presence of particular hormonal disorders and other chronic diseases or as a result of medications, specifically glucocorticoids, when the disease is called steroid- or glucocorticoid-induced osteoporosis (SIOP or GIOP). Given its influence on the risk of fragility fracture, osteoporosis may significantly affect life expectancy and quality of life.

Osteoporosis can be prevented with lifestyle advice and sometimes medication, and in people with osteoporosis treatment may involve lifestyle advice, preventing falls and medication (calcium, vitamin D, bisphosphonates and several others).

Signs and symptoms

Osteoporosis itself has no specific symptoms; its main consequence is the increased risk of bone fractures. Osteoporotic fractures are those that occur in situations where healthy people would not normally break a bone; they are therefore regarded as fragility fractures. Typical fragility fractures occur in the vertebral column, hip and wrist.

Fractures

The symptoms of a vertebral collapse ("compression fracture") are sudden back pain, often with radiculopathic pain (shooting pain due to compression of a nerve) and rarely with spinal cord compression or cauda equina syndrome. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility.[2]

Fractures of the long bones acutely impair mobility and may require surgery. Hip fracture, in particular, usually requires prompt surgery, as there are serious risks associated with a hip fracture, such as deep vein thrombosis and a pulmonary embolism, and increased mortality.

Falls risk

The increased risk of falling associated with aging leads to fractures of the wrist, spine and hip. The risk of falling, in turn, is increased by impaired eyesight due to any cause (e.g. glaucoma, macular degeneration), balance disorder, movement disorders (e.g. Parkinson's disease), dementia, and sarcopenia (age-related loss of skeletal muscle). Collapse (transient loss of postural tone with or without loss of consciousness) leads to a significant risk of falls; causes of syncope are manifold but may include cardiac arrhythmias (irregular heart beat), vasovagal syncope, orthostatic hypotension (abnormal drop in blood pressure on standing up) and seizures. Removal of obstacles and loose carpets in the living environment may substantially reduce falls. Those with previous falls, as well as those with a gait or balance disorder, are most at risk.[3]

Risk factors

Risk factors for osteoporotic fracture can be split between non-modifiable and (potentially) modifiable. In addition, there are specific diseases and disorders in which osteoporosis is a recognized complication. Medication use is theoretically modifiable, although in many cases the use of medication that increases osteoporosis risk is unavoidable.

Nonmodifiable

The most important risk factors for osteoporosis are advanced age (in both men and women) and female sex; estrogen deficiency following menopause is correlated with a rapid reduction in BMD, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect. While osteoporosis occurs in people from all ethnic groups, European or Asian ancestry predisposes for osteoporosis.[4] Those with a family history of fracture or osteoporosis are at an increased risk; the heritability of the fracture as well as low bone mineral density are relatively high, ranging from 25 to 80 percent. There are at least 30 genes associated with the development of osteoporosis.[5] Those who have already had a fracture are at least twice as likely to have another fracture compared to someone of the same age and sex.[6]

Potentially modifiable

  • Tobacco smoking - tobacco smoking inhibits the activity of osteoblasts, and is an independent risk factor for osteoporosis.[7]
  • Low body mass index - being overweight protects against osteoporosis, either by increasing load or through the hormone leptin.[8]
  • Malnutrition
  • Excess alcohol - small amounts of alcohol do not increase osteoporosis risk and may even be beneficial, but chronic heavy drinking, especially at a younger age, increases risk significantly.[9]
  • Insufficient physical activity - bone performs remodeling in response to physical stress. People who remain physically active throughout life have a lower risk of osteoporosis. The kind of physical activity that have most effects on bone are weight bearing exercises. The bony prominences and attachments in runners are different in shape and size than those in weightlifters. Physical activity has its greatest impact during adolescence, affecting peak bone mass most. In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%. Physical fitness in later life is associated more with a decreased risk of falling than with an increased bone mineral density. Conversely, people who are bedridden are at a significantly increased risk.
  • Excess physical activity - excessive exercise can lead to constant damages to the bones which can cause exhaustion of the structures as described above. There are numerous examples of marathon runners who developed severe osteoporosis later in life. In females, heavy exercise leads to amenorrhea (suppression of the menstrual cycle), which is associated with decreased estrogen levels.
  • Heavy metals - a strong association between cadmium, lead and bone disease has been established. Low level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders, leading to pain and increased risk of fractures, especially in elderly and in females. Higher cadmium exposure results in osteomalacia (softening of the bone).[10]
  • Soft drinks - some studies indicate that soft drinks (many of which contain phosphoric acid) may increase risk of osteoporosis;[11] others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.[12]

Diseases and disorders

There are many disorders associated with osteoporosis:

Medication

Certain medications have been associated with an increase in osteoporosis risk; only steroids and anticonvulsants are classically associated; evidence is emerging with regard to other drugs:

  • Steroid-induced osteoporosis (SIOP) arises due to use of glucocorticoids - analogous to Cushing's syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug prednisone is a main candidate after prolonged intake. Some professional guidelines recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months.[13]
  • Barbiturates and some other enzyme-inducing antiepileptics - these probably accelerate the metabolism of vitamin D. [14]
  • Proton pump inhibitors - these drugs inhibit the production of stomach acid; it is thought that this interferes with calcium absorption.[15]
  • Anticoagulants - long-term use of heparin is associated with a decrease in bone density,[16] and warfarin (and related coumarins) have been linked with an increased risk in osteoporotic fracture in long-term use.[17]
  • Thiazolidinediones (used for diabetes) - rosiglitazone and possibly pioglitazone, inhibitors of PPARγ, have been linked with an increased risk of osteoporosis and fracture.[18]

Diagnosis

A scanner used to measure bone density with dual energy X-ray absorptiometry.

The diagnosis of osteoporosis is made on measuring the bone mineral density (BMD). The most popular method is dual energy X-ray absorptiometry (DXA or DEXA). In addition to the detection of abnormal BMD, the diagnosis of osteoporosis requires investigations into potentially modifiable underlying causes; this may be done with blood tests and X-rays. Depending on the likelihood of an underlying problem, investigations for cancer with metastasis to the bone, multiple myeloma, Cushing's disease and other above mentioned causes may be performed.

Dual energy X-ray absorptiometry

Dual energy X-ray absorptiometry (DXA, formerly DEXA) is considered the gold standard for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established the following diagnostic guidelines:[1][19]

  • T-score -1.0 or greater is "normal"
  • T-score between -1.0 and -2.5 is "low bone mass" (or "osteopenia")
  • T-score -2.5 or below is osteoporosis

When there has also been an osteoporotic fracture (also termed "low trauma-fracture" or "fragility fracture"), defined as one that occurs as a result of a fall from a standing height, the term "severe or established" osteoporosis is used.[1]

Screening

The U.S. Preventive Services Task Force (USPSTF) recommended in 2002 that all women 65 years of age or older should be screened with bone densitometry.[20] The Task Force recommends screening only those women ages 60 to 64 years of age who are at increased risk. The best risk factor for indicating increased risk is lower body weight (weight < 70 kg), with less evidence for smoking or family history. There was insufficient evidence to make recommendations about the optimal intervals for repeated screening and the appropriate age to stop screening. Clinical prediction rules are available to guide selection of women ages 60-64 for screening. The Osteoporosis Risk Assessment Instrument (ORAI) may be the most sensitive strategy[21]

Regarding the screening of men, a cost-analysis study suggests that screening may be "cost-effective for men with a self-reported prior fracture beginning at age 65 years and for men 80 years and older with no prior fracture".[22]

Pathogenesis

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. In normal bone, there is constant matrix remodeling of bone; up to 10% of all bone mass may be undergoing remodeling at any point in time. The process takes place in bone multicellular units (BMUs) as first described by Frost in 1963.[23] Bone is resorbed by osteoclast cells (which derive from the bone marrow), after which new bone is deposited by osteoblast cells. [5]

The three main mechanisms by which osteoporosis develops are an inadequate peak bone mass (the skeleton develops insufficient mass and strength during growth), excesive bone resorption and inadequate formation of new bone during remodeling. An interplay of these three mechanisms underlies the development of fragile bone tissue.[5] Hormonal factors strongly determine the rate of bone resorption; lack of estrogen (e.g. as a result of menopause) increases bone resorption as well as decreasing the deposition of new bone that normally takes place in weight-bearing bones. The amount of estrogen needed to suppress this process is lower than that normally needed to stimulate the uterus and breast gland. The α-form of the estrogen receptor appears to be the most important in regulating bone turnover.[5] In addition to estrogen, calcium metabolism plays a significant role in bone turnover, and deficiency of calcium and vitamin D leads to impaired bone deposition; in addition, the parathyroid glands react to low calcium levels by secreting parathyroid hormone (parathormone, PTH), which increases bone resorption to ensure sufficient calcium in the blood. The role of calcitonin, a hormone generated by the thyroid that increases bone deposition, is less clear and probably not as significant as that of PTH.[5]

The activation of osteoclasts is regulated by various molecular signals, of which RANKL (receptor activator for nuclear factor κB ligand) is one of best studied. This molecule is produced by osteoblasts and other cells (e.g. lymphocytes), and stimulates RANK (receptor activator of nuclear factor κB). Osteoprotegerin (OPG) binds RANKL before it has an opportunity to bind to RANK, and hence suppresses its ability to increase bone resorption. RANKL, RANK and OPG are closely related to tumor necrosis factor and its receptors. The role of the wnt signalling pathway is recognized but less well understood. Local production of eicosanoids and interleukins is thought to participate in the regulation of bone turnover, and excess or reduced production of these mediators may underlie the development of osteoporosis.[5]

Trabecular bone is the sponge-like bone in the ends of long bones and vertebrae. Cortical bone is the hard outer shell of bones and the middle of long bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Not only is bone density decreased, but the microarchitecture of bone is disrupted. The weaker spicules of trabecular bone break ("microcracks"), and are replaced by weaker bone. Common osteoporotic fracture sites, the wrist, the hip and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on trabecular bone for strength, and therefore the intense remodeling causes these areas to degenerate most when the remodeling is imbalanced.[citation needed]

Treatment

There are several alternatives of medication to treat osteoporosis, though lifestyle changes are very frequently an aspect of treatment.

Medication

Bisphosphonates are the main pharmacological measures for treatment. However, newer drugs have appeared in the 1990s, such as teriparatide and strontium ranelate.

Bisphosphonates

In confirmed osteoporosis, bisphosphonate drugs are the first-line treatment. The most often prescribed bisphosphonates are presently sodium alendronate (Fosamax) 10 mg a day or 70 mg once a week, risedronate (Actonel) 5 mg a day or 35 mg once a week and or ibandronate (Boniva) once a month.

A 2007 manufacturer-supported study suggested that in patients who had suffered a low-impact hip fracture, annual infusion of 5 mg zoledronic acid reduced risk of any fracture by 35% (from 13.9 to 8.6%), vertebral fracture risk from 3.8% to 1.7% and non-vertebral fracture risk from 10.7% to 7.6%. This study also found a mortality benefit: after 1.9 years, 9.6% of the study group (as opposed to 13.3% of the control group) had died of any cause, indicating a mortality benefit of 28%.[24]

Oral bisphosphonates are relatively poorly absorbed, and must therefore be taken on an empty stomach, with no food or drink to follow for the next 30 minutes. They are associated with esophagitis and are therefore sometimes poorly tolerated; weekly or monthly administration (depending on the preparation) decreases likelihood of esophagitis, and is now standard. Although intermittent dosing with the intravenous formulations such as zolendronate avoids oral tolerance problems, these agents are implicated at higher rates in a rare but unpleasant mouth disease called osteonecrosis of the jaw.[25] For this reason, oral bisphosphonate therapy is probably to be preferred, and prescribing advice now recommends any remedial dental work to be carried out prior to commencing treatment.[26]

Teriparatide

Recently, teriparatide (Forteo, recombinant parathyroid hormone residues 1–34) has been shown to be effective in osteoporosis. It is used mostly for patients with established osteoporosis (who have already fractured), have particularly low BMD or several risk factors for fracture or cannot tolerate the oral bisphosphonates. It is given as a daily injection with the use of a pen-type injection device. Teriparatide is only licensed for treatment if bisphosphonates have failed or are contraindicated (however, this differs by country and is not required by the FDA in the USA. However, patients with previous radiation therapy, or Paget's disease, or young patients should avoid this medication).

Strontium ranelate

Oral strontium ranelate is an alternative oral treatment, belonging to a class of drugs called "dual action bone agents" (DABAs) by its manufacturer. It has proven efficacy, especially in the prevention of vertebral fracture.[27] In laboratory experiments, strontium ranelate was noted to stimulate the proliferation of osteoblasts, as well as inhibiting the proliferation of osteoclasts.

Strontium ranelate is taken as a 2 g oral suspension daily, and is licenced for the treatment of osteoporosis to prevent vertebral and hip fracture. Strontium ranelate has side effect benefits over the bisphosphonates, as it does not cause any form of upper GI side effect, which is the most common cause for medication withdrawal in osteoporosis. In studies a small increase in the risk of venous thromboembolism was noted,[28] the cause for which has not been determined. This suggests it may be less suitable in patients at risk for thrombosis for different reasons. The uptake of (heavier) strontium in place of calcium into bone matrix results in a substantial and disproportionate increase in bone mineral density as measured on DXA scanning[29], making further followup of bone density by this method unhelpful for strontium treated patients.

Nutrition

Calcium

Calcium is required to support bone growth, bone healing and maintain bone strength and is one aspect of treatment for osteoporosis. Recommendations for calcium intake vary depending country and age; for individuals at higher risk of osteoporosis (after fifty years of age) the amount recommended by US health agencies is 1,200 mg per day. Calcium supplements can be used to increase dietary intake, and absorption is optimized through taking in several small (500 mg or less) doses throughout the day.[30] The role of calcium in preventing and treating osteoporosis is unclear - some populations with extremely low calcium intake also have extremely low rates of bone fracture, and others with high rates of calcium intake through milk and milk products have higher rates of bone fracture. Other factors, such as protein, salt and vitamin D intake, exercise and esposure to sunlight, can all influence bone mineralization, making calcium intake one factor among many in the development of osteoporosis.[31]

A meta-analysis of randomized controlled trials involving calcium and calcium plus vitamin D supported the use of high levels of calcium (1,200 mg or more) and vitamin D (800 IU or more), though outcomes varied depending on which measure was used to assess bone health (rates of fracture versus rates of bone loss).[32] The meta-analysis, along with another study, also supported much better outcomes for patients with high compliance to the treatment protocol.[33] In contrast, despite earlier reports in improved high density lipoprotein (HDL, "good cholesterol") in calcium supplementation, a possible increase in the rate of myocardial infarction (heart attack) was found in a study in New Zealand in which 1471 women participated. If confirmed, this would indicate that calcium supplementation in women otherwise at low risk of fracture may cause more harm than good.[34]

Vitamin D

Some studies have shown that a high intake of vitamin D reduces fractures in the elderly,[32][35] though the Women's Health Initiative found that though calcium plus vitamin D did increase bone density, it did not affect hip fracture but did increase formation of kidney stones.[36]

Mechanical stimulation

Exercise

Multiple studies have shown that aerobics, weight bearing, and resistance exercises can all maintain or increase BMD in postmenopausal women.[37] Many researchers have attempted to pinpoint which types of exercise are most effective at improving BMD and other metrics of bone quality, however results have varied. One year of regular jumping exercises appears to increase the BMD and moment of inertia of the proximal tibia[38] in normal postmenopausal women. Treadmill walking, gymnastic training, stepping, jumping, endurance, and strength exercises all resulted in significant increases of L2-L4 BMD in osteopenic postmenopausal women.[39][40][41] Strength training elicited improvements specifically in distal radius and hip BMD.[42] Exercise combined with other pharmacological treatments such as hormone replacement therapy (HRT) has been shown to increases BMD more than HRT alone.[43]

Additional benefits for osteoporotic patients other than BMD increase include improvements in balance, gait, and a reduction in risk of falls.[44]

Low-level mechanical signals

Low-level high-frequency mechanical signals have been studied as signals stimulating bone turnover. Studies in animals show that this form of 'passive exercise' results in increased bone strength. Preliminary studies in humans (using for example vibrating platforms to produce whole body vibration) indicate that they might prevent BMD loss.[45] [46][47][48]

Prognosis

Hip fractures per 1000 patient-years[49]
WHO category Age 50-64 Age > 64 Overall
Normal 5.3 9.4 6.6
Osteopenia 11.4 19.6 15.7
Osteoporosis 22.4 46.6 40.6

Although osteoporosis patients have an increased mortality rate due to the complications of fracture, most patients die with the disease rather than of it.

Hip fractures can lead to decreased mobility and an additional risk of numerous complications (such as deep venous thrombosis and/or pulmonary embolism, pneumonia). The 6-month mortality rate following hip fracture is approximately 13.5%, and a substantial proportion (almost 13%) of people who have suffered a hip fracture need total assistance to mobilize after a hip fracture.[50]

Vertebral fractures, while having a smaller impact on mortality, can lead to severe chronic pain of neurogenic origin, which can be hard to control, as well as deformity. Though rare, multiple vertebral fractures can lead to such severe hunch back (kyphosis) that the resulting pressure on internal organs can impair one's ability to breathe.

Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced health-related quality of life.[51]

Epidemiology

It is estimated[citation needed] that 1 in 3 women and 1 in 12 men over the age of 50 worldwide have osteoporosis. It is responsible for millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist. Fragility fractures of ribs are also common in men.

Hip fractures

Hip fractures are responsible for the most serious consequences of osteoporosis. In the United States, osteoporosis causes a predisposition to hip fractures -- more than 250,000 occur annually. It is estimated that a 50-year-old white woman has a 17.5% lifetime risk of fracture of the proximal femur. The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations. The highest incidence is found among those men and women ages 80 or older.[citation needed]

Vertebral fractures

Between 35-50% of all women over 50 had at least one vertebral fracture. In the United States, 700,000 vertebral fractures occur annually, but only about a third are recognized. In a series of 9704 of women aged 68.8 on average studied for 15 years, 324 had already suffered a vertebral fracture at entry into the study; 18.2% developed a vertebral fracture, but that risk rose to 41.4% in women who had a previous vertebral fracture.[52]

Distal radius fractures

Distal radius fractures, usually of the Colles type, are the third most common type of osteoporotic fractures. In the United States, the total annual number of Colles' fractures is about 250,000. The lifetime risk of sustaining a Colles' fracture is about 16% for white women. By the time women reach age 70, about 20% have had at least one wrist fracture.[citation needed]

Prevention

Methods to prevent osteoporosis include changes of lifestyle. However, there are medications that can be used for prevention as well. Fall prevention can help prevent osteoporosis complications.

Lifestyle

Lifestyle prevention of osteoporosis is in many aspects inversions from potentially modifiable risk factors. As tobacco smoking and unsafe alcohol intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended in the prevention of osteoporosis.[citation needed]

Exercise

Achieving a higher peak bone mass through exercise and proper nutrition during adolescence is important for the prevention of osteoporosis. Exercise and nutrition throughout the rest of the life delays bone degeneration. Jogging, walking, or stair climbing at 70-90% of maximum effort three times per week, along with 1,500 mg of calcium per day, increased bone density of the lumbar (lower) spine by 5% over 9 months. Individuals already diagnosed with osteopenia or osteoporosis should discuss their exercise program with their physician to avoid fractures.[53]

Nutrition

A proper nutrition is a diet sufficient in calcium and vitamin D. Patients at risk for osteoporosis (e.g. steroid use) are generally treated with vitamin D and calcium supplements and often with bisphosphonates. In renal disease, more active forms of Vitamin D such as paracalcitol or (1,25-dihydroxycholecalciferol or calcitriol which is the main biologically active form of vitamin D) is used, as the kidney cannot adequately generate calcitriol from calcidiol (25-hydroxycholecalciferol) which is the storage form of vitamin D.

High dietary protein intake increases calcium excretion in urine and has been linked to increased risk of fractures in research studies.[54] Other investigations have shown that protein is required for calcium absorption, but that excessive protein consumption inhibits this process. No interventional trials have been performed on dietary protein in the prevention and treatment of osteoporosis.[55]

Medication

Just as for treatment, bisphosphonate can be used in cases of very high risk. Other medicines prescribed for prevention of osteoporosis include raloxifene (Evista), a selective estrogen receptor modulator (SERM).

Estrogen replacement remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause; hopefully new research will provide guidance. In men, testosterone replacement therapy is also an effective treatment.

History

The link between age-related reductions in bone density and fracture risk goes back at least to Astley Cooper, and the term "osteoporosis" and recognition of its pathological appearance is generally attributed to the French pathologist Jean Lobstein.[56] The American endocrinolgist Fuller Albright linked osteoporosis with the postmenopausal state.[57] Bisphosponates, which revolutionized the treatment of osteoporosis, were discovered in the 1960s.[58]

See also

References

  1. ^ a b c WHO (1994). "Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group". World Health Organization technical report series. 843: 1–129. PMID 7941614.
  2. ^ Kim DH, Vaccaro AR (2006). "Osteoporotic compression fractures of the spine; current options and considerations for treatment". The spine journal : official journal of the North American Spine Society. 6 (5): 479–87. doi:10.1016/j.spinee.2006.04.013. PMID 16934715.
  3. ^ Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ (2007). "Will my patient fall?". JAMA. 297 (1): 77–86. doi:10.1001/jama.297.1.77. PMID 17200478.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Melton LJ (2003). "Epidemiology worldwide". Endocrinol. Metab. Clin. North Am. 32 (1): 1–13, v. PMID 12699289.
  5. ^ a b c d e f Raisz L (2005). "Pathogenesis of osteoporosis: concepts, conflicts, and prospects". J Clin Invest. 115 (12): 3318–25. doi:10.1172/JCI27071. PMID 16322775.
  6. ^ Ojo F, Al Snih S, Ray LA, Raji MA, Markides KS (2007). "History of fractures as predictor of subsequent hip and nonhip fractures among older Mexican Americans". Journal of the National Medical Association. 99 (4): 412–8. PMID 17444431.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Wong PK, Christie JJ, Wark JD (2007). "The effects of smoking on bone health". Clin. Sci. 113 (5): 233–41. doi:10.1042/CS20060173. PMID 17663660.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Shapses SA, Riedt CS (2006). "Bone, body weight, and weight reduction: what are the concerns?". J. Nutr. 136 (6): 1453–6. PMID 16702302.
  9. ^ Sampson HW (2002). "Alcohol and other factors affecting osteoporosis risk in women". Alcohol Res Health. 26 (4): 292–8. PMID 12875040.
  10. ^ Staessen J, Roels H, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R (1999). "Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group". Lancet. 353 (9159): 1140–4. PMID 10209978. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP (2006). "Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study". Am. J. Clin. Nutr. 84 (4): 936–42. PMID 17023723.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ "Soft drinks in schools". Pediatrics. 113 (1 Pt 1): 152–4. 2004. PMID 14702469.
  13. ^ Bone and Tooth Society of Great Britain, National Osteoporosis Society, Royal College of Physicians (2003). Glucocorticoid-induced Osteoporosis (PDF). London, UK: Royal College of Physicians of London. ISBN 1-860-16173-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
  14. ^ Petty SJ, O'Brien TJ, Wark JD (2007). "Anti-epileptic medication and bone health". Osteoporosis international. 18 (2): 129–42. doi:10.1007/s00198-006-0185-z. PMID 17091219.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Yang YX, Lewis JD, Epstein S, Metz DC (2006). "Long-term proton pump inhibitor therapy and risk of hip fracture". JAMA. 296: 2947–53. PMID 17190895.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Ruiz-Irastorza G, Khamashta MA, Hughes GR (2002). "Heparin and osteoporosis during pregnancy: 2002 update". Lupus. 11 (10): 680–2. PMID 12413068.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF (2006). "Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2". Arch. Intern. Med. 166 (2): 241–6. doi:10.1001/archinte.166.2.241. PMID 16432096.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ Murphy CE, Rodgers PT (2007). "Effects of thiazolidinediones on bone loss and fracture". Ann Pharmacother. 41 (12): 2014–8. doi:10.1345/aph.1K286. PMID 17940125.
  19. ^ WHO Scientific Group on the Prevention and Management of Osteoporosis (2000 : Geneva, Switzerland) (2003). "Prevention and management of osteoporosis : report of a WHO scientific group" (pdf). Retrieved 2007-05-31.{{cite web}}: CS1 maint: numeric names: authors list (link)
  20. ^ U.S. Preventive Services Task Force (2002). "Screening for osteoporosis in postmenopausal women: recommendations and rationale". Ann. Intern. Med. 137 (6): 526–8. PMID 12230355.
  21. ^ Martínez-Aguilà D, Gómez-Vaquero C, Rozadilla A, Romera M, Narváez J, Nolla JM (2007). "Decision rules for selecting women for bone mineral density testing: application in postmenopausal women referred to a bone densitometry unit". J. Rheumatol. 34 (6): 1307–12. PMID 17552058.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Schousboe JT, Taylor BC, Fink HA; et al. (2007). "Cost-effectiveness of bone densitometry followed by treatment of osteoporosis in older men". JAMA. 298 (6): 629–37. doi:10.1001/jama.298.6.629. PMID 17684185. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  23. ^ Frost HM, Thomas CC. Bone Remodeling Dynamics. Springfield, IL: 1963.
  24. ^ Lyles KW, Colón-Emeric CS, Magaziner JS; et al. (2007). "Zoledronic acid and clinical fractures and mortality after hip fracture". N Engl J Med: published online 2007-09-17. doi:10.1056/NEJMoa074941. PMID 17878149. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  25. ^ Purcell, P. Boyd, I (2005). "Bisphosphonates and osteonecrosis of the jaw". Medical Journal of Australia. 182 (8): 417–418.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ "6.6.2 Bisphosphonates". British National Formulary (54 ed.). British Medical Association and Royal Pharmaceutical Society of Great Britain. September 2007. pp. p403. {{cite book}}: |pages= has extra text (help)
  27. ^ Meunier PJ, Roux C, Seeman E; et al. (2004). "The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis". N. Engl. J. Med. 350 (5): 459–68. doi:10.1056/NEJMoa022436. PMID 14749454. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  28. ^ O'Donnell S, Cranney A, Wells GA, Adachi JD, Reginster JY (2006). "Strontium ranelate for preventing and treating postmenopausal osteoporosis". Cochrane database of systematic reviews (Online) (4): CD005326. doi:10.1002/14651858.CD005326.pub3. PMID 17054253.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Reginster JY, Seeman E, De Vernejoul MC; et al. (2005). "Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study". J Clin Endorinol Metab. 90: 2816–22. PMID 15728210. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  30. ^ "Nutrition and Bone Health". NIAMS. 2005-11-01. Retrieved 2008-01-28.
  31. ^ "Calcium & Milk". Harvard School of Public Health. 2007. Retrieved 2008-01-28.
  32. ^ a b Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A (2007). "Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis". Lancet. 370 (9588): 657–66. doi:10.1016/S0140-6736(07)61342-7. PMID 17720017.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Prince RL, Devine A, Dhaliwal SS, Dick IM (2006). "Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women". Arch. Intern. Med. 166 (8): 869–75. doi:10.1001/archinte.166.8.869. PMID 16636212.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ Bolland MJ, Barber PA, Doughty RN; et al. (2008). "Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial". BMJ. doi:10.1136/bmj.39440.525752.BE. PMID 18198394. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  35. ^ Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005). "Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials". JAMA. 293 (18): 2257–64. doi:10.1001/jama.293.18.2257. PMID 15886381.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  36. ^ Jackson RD, LaCroix AZ, Gass M; et al. (2006). "Calcium plus vitamin D supplementation and the risk of fractures". N. Engl. J. Med. 354 (7): 669–83. doi:10.1056/NEJMoa055218. PMID 16481635. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  37. ^ Bonaiuti D, Shea B, Iovine R; et al. (2002). "Exercise for preventing and treating osteoporosis in postmenopausal women". Cochrane database of systematic reviews (Online) (3): CD000333. PMID 12137611. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  38. ^ Cheng S, Sipilä S, Taaffe DR, Puolakka J, Suominen H (2002). "Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women". Bone. 31 (1): 126–35. PMID 12110425.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  39. ^ Chien MY, Wu YT, Hsu AT, Yang RS, Lai JS (2000). "Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women". Calcif. Tissue Int. 67 (6): 443–8. PMID 11289692.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  40. ^ Iwamoto J, Takeda T, Ichimura S (2001). "Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis". Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 6 (2): 128–32. doi:10.1007/s0077610060128. PMID 11484097.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  41. ^ Kemmler W, Engelke K, Weineck J, Hensen J, Kalender WA (2003). "The Erlangen Fitness Osteoporosis Prevention Study: a controlled exercise trial in early postmenopausal women with low bone density-first-year results". Archives of physical medicine and rehabilitation. 84 (5): 673–82. PMID 12736880.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Kerr D, Morton A, Dick I, Prince R (1996). "Exercise effects on bone mass in postmenopausal women are site-specific and load-dependent". J. Bone Miner. Res. 11 (2): 218–25. PMID 8822346.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  43. ^ Villareal DT, Binder EF, Yarasheski KE; et al. (2003). "Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women". J Am Geriatr Soc. 51 (7): 985–90. PMID 12834519. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  44. ^ Sinaki M, Brey RH, Hughes CA, Larson DR, Kaufman KR (2005). "Significant reduction in risk of falls and back pain in osteoporotic-kyphotic women through a Spinal Proprioceptive Extension Exercise Dynamic (SPEED) program". Mayo Clin Proc. 80 (7): 849–55. PMID 16007888.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  45. ^ Rubin C, Judex S, Qin YX (2006). "Low-level mechanical signals and their potential as a non-pharmacological intervention for osteoporosis" (PDF). Age Ageing. 35 Suppl 2: ii32-ii36. PMID 16926201.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  46. ^ Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C (2006). "Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD". J Bone Miner Res. 21 (9): 1464–74. PMID 16939405.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  47. ^ Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z (2004). "Low magnitude mechanical loading is osteogenic in children with disabling conditions". J Bone Miner Res. 19 (3): 360–9. PMID 15040823.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  48. ^ Beck BR, Kent K, Holloway L, Marcus R (2006). "Novel, high-frequency, low-strain mechanical loading for premenopausal women with low bone mass: early findings". J Bone Miner Metab. 24 (6): 505–7. PMID 17072744.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ Cranney A, Jamal SA, Tsang JF, Josse RG, Leslie WD (2007). "Low bone mineral density and fracture burden in postmenopausal women". CMAJ. 177 (6): 575–80. doi:10.1503/cmaj.070234. PMID 17846439.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  50. ^ Hannan EL, Magaziner J, Wang JJ; et al. (2001). "Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes". JAMA. 285 (21): 2736–42. PMID 11386929. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  51. ^ Brenneman SK, Barrett-Connor E, Sajjan S, Markson LE, Siris ES (2006). "Impact of recent fracture on health-related quality of life in postmenopausal women". J. Bone Miner. Res. 21 (6): 809–16. doi:10.1359/jbmr.060301. PMID 16753011.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  52. ^ Cauley JA, Hochberg MC, Lui LY; et al. (2007). "Long-term Risk of Incident Vertebral Fractures". JAMA. 298: 2761–2767. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  53. ^ Dalsky GP, Stocke KS, Ehsani AA, Slatopolsky E, Lee WC, Birge SJ (1988). "Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women". Ann. Intern. Med. 108 (6): 824–8. PMID 3259410.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  54. ^ Feskanich D, Willett WC, Stampfer MJ, Colditz GA (1996). "Protein consumption and bone fractures in women". Am. J. Epidemiol. 143 (5): 472–9. PMID 8610662.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  55. ^ Kerstetter JE, O'Brien KO, Insogna KL (2003). "Dietary protein, calcium metabolism, and skeletal homeostasis revisited". Am. J. Clin. Nutr. 78 (3 Suppl): 584S–592S. PMID 12936953.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  56. ^ Lobstein JGCFM. Lehrbuch der pathologischen Anatomie. Stuttgart: Bd II, 1835.
  57. ^ Albright F, Bloomberg E, Smith PH (1940). "Postmenopausal osteoporosis". Trans. Assoc. Am. Physicians. 55: 298–305. {{cite journal}}: Cite has empty unknown parameter: |month= (help)CS1 maint: multiple names: authors list (link)
  58. ^ Patlak M (2001). "Bone builders: the discoveries behind preventing and treating osteoporosis". FASEB J. 15 (10): 1677E–E. PMID 11481214.

Template:Link FA

  1. ^ Cite error: The named reference pmid17552058 was invoked but never defined (see the help page).
Retrieved from "https://en.wikipedia.org/w/index.php?title=Osteoporosis&oldid=198004943"